This project examines the functional neuroanatomical organization of the forebrain, in particular the cerebral cortex and basal ganglia. Quantitative in situ hybridization histochemistry is used to measure levels of mRNAs encoding transcription factors and neurochemicals, including neurotransmitter receptors, peptides and signal transduction proteins, which are expressed by connectionally identified neurons in the striatum. Receptor-mediated changes in gene regulation in striatal output neurons are used to study adaptive changes in cortical-basal ganglia function. Studies completed during the past year have focused on synergism between D1 and D2 dopamine receptors mediated by interneuronal interactions, the affects of glutamate receptor blockade on dopamine function, and the role of the opiate peptide dynorphin in the adaptive response of striatal neurons to dopamine hyperactivation produced by cocaine. Findings advance models of neurologic disease and mental disorders, including Parkinson's disease, attention deficit hyperactivity disorder (ADHD), schizophrenia, and psychostimulant drug abuse.